Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) is increasingly being used worldwide as part of the clinical workup for men with prostate cancer. With high overall accuracy for the detection of prostate cancer, PSMA-targeted PET has an increasingly established role in the setting of biochemical failure after primary therapy and an evolving role in the setting of initial disease staging; its utility for guiding management in the setting of metastatic disease is less clear. Although the specificity is high, familiarization with potential pitfalls in the interpretation of PSMA-targeted PET, including knowledge of the causes for false positive and negative examinations, is critical. The aim of this article is to provide an illustrative discussion of the current and evolving clinical indications for PSMA-targeted PET, as well as a review of physiologic radiopharmaceutical biodistribution and potential imaging pitfalls.

Introduction: Differentiation of renal cell carcinoma (RCC) from oncocytoma is a common diagnostic dilemma. A few studies have shown that 99mTc-sestamibi (MIBI) imaging has the potential to characterize indeterminate renal masses. This comparative study evaluated the utility of MIBI single-photon emission computed tomography-computed tomography (SPECT-CT) in the assessment and risk stratification of renal masses. Methods: A total of 29 patients with 31 renal masses who had cross-sectional imaging and MIBI SPECT-CT, were included. Lesions were categorized as either MIBI-positive or -negative on SPECT-CT. Individual lesion density ranged from 22–56 Hounsfield Units (HU) on the non-contrast CT part of SPECT-CT. Quantitative relative MIBI uptake was calculated by measuring tumor to ipsilateral renal parenchymal uptake. The imaging results were correlated with histopathology. Results: All oncocytic lesions, including seven oncocytomas and one hybrid oncocytic chromophobe tumor (100%), were positive on MIBI. One chromophobe RCC showed low-grade MIBI uptake. The remaining RCC subtypes, including 15 clear-cell, four papillary, two mixed clear-cell and papillary, and one chromophobe were MIBI-negative. The quantitative relative tumor uptake showed statistically significant higher uptake in the low-risk/oncocytic lesions compared to RCCs. Conclusions: This study demonstrates that MIBI SPECT-CT is valuable in the characterization of indeterminate renal masses. The combination of MIBI uptake on SPECT and lesion density on non-contrast CT can be used for risk stratification of renal masses. This technique may reduce the need for further imaging (multiphasic CT or magnetic resonance imaging), renal mass biopsy, or surgical resection of low-risk renal masses. Subsequently, more patients could be followed with active surveillance.

Purpose 177Lu-Dotatate is an emerging treatment modality for patients with unresectable or metastatic well-differentiated NETs. This study examines survival predictors in patients who received 177Lu-Dotatate. Methods A retrospective single-center review was conducted, examining 47 individuals with progressive well-differentiated NETs treated with 177Lu-Dotatate (four induction cycles of 5.5 GBq at 10-week intervals followed by eight maintenance cycles of 3.7 GBq at 6-month intervals). Results Median follow-up was 63.1 months with a median progression-free survival (PFS) of 34.1 months. However, median overall survival (OS) was not reached at the time of analysis. The presence of ≥ 5 bone metastases (hazard ratio HR 4.33; p = 0.015), non-gastroenteropancreatic (non-GEP) NETs (HR 3.22; p = 0.025) and development of interim ascites (HR 3.15; p = 0.047) independently predicted a worse OS. Patients with chromogranin A of ≥ 4 × upper limit of normal (ULN) had shorter OS (p < 0.001) and PFS (p = 0.004). Similarly, those with pre-existing ascites demonstrated a worse OS (p = 0.009) and PFS (p = 0.026). Liver metastases involving greater than 50% liver volume and the existence of unusual metastatic locations had a negative impact on OS (p = 0.033) and PFS (p = 0.026), respectively. Conclusion High burden of skeletal and hepatic metastases, non-GEP-NETs, chromogranin A of ≥ 4 × ULN, unusual metastatic sites, pre-existing and interim ascites are predictors of poor outcomes in patients treated with 177Lu-Dotatate. These common indicators can be used for the risk stratification and identification of patients most likely to benefit from PRRT. Trial registration ClinicalTrials.gov identifier: NCT02236910, Retrospectively registered on September, 2014.

Peptide receptor radionuclide therapy (PRRT) has been recently established as a treatment option for progressive gastro-entero-pancreatic neuroendocrine tumors (NETs) including four 200 mCi induction cycles. The purpose of this phase 2 trial is to expand use of PRRT to different types of NETs with the application of dose adjustment and evaluate value of maintenance therapy in patients who had disease control on induction therapy. Forty-seven PRRT naïve NET patients with different primary origin received 177Lu-DOTATATE induction therapy, ranging from 75 to 150 mCi per cycle, based on patients’ clinical status such as liver and renal function, extent of metastases, and previous therapies. Thirty-four patients underwent additional maintenance therapy (50–100 mCi per cycle) following induction course until they developed disease progression. The estimated median progression-free survival (PFS) was 36.1 months. The median PFS in our MNET subgroup was 47.7 months, which is markedly longer than NETTER-1 trial with median PFS of 28.4 months. The median PFS was significantly longer in patients who received PRRT as first-line treatment after disease progression on somatostatin analogs compared to patients who received other therapies first (p-value = 0.04). The total disease response rate (DRR) and disease control rate (DCR) was 32% and 85% based on RECIST 1.1 and 45% and 83% based on Choi criteria. This trial demonstrates longer PFS with the addition of low dose maintenance therapy to induction therapy compared to NETTER-1 trial that only included induction therapy. Also, we observed considerable efficacy of PRRT in various types of advanced NETs.

Prostate Specific Membrane Antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is becoming established as a standard of care for the (re)staging of high-risk primary and prostate cancer recurrence after primary therapy. Despite the favorable performance of this imaging modality with high accuracy in disease detection, the availability of PSMA PET/CT varies across jurisdictions worldwide due to variability in the selection of PSMA PET/CT agent, regulatory approvals and funding. In Canada, PSMA based radiopharmaceuticals are still considered investigational new drug (IND), creating limitations in the deployment of these promising imaging agents. While regulatory approval rests with Health Canada, as a single payer health system, funding for Health Canada approved drugs and devices is decided by Provincial Health Ministries. Ontario Health (Cancer Care Ontario) (OH-CCO) is the agency of the Ministry of Health (MOH) in Ontario responsible for making recommendations to the MOH around the organization and funding of cancer services within Ontario (population of 15 million), and the PET Steering Committee of OH-CCO is responsible for providing recommendations on the introduction of new PET radiopharmaceuticals and indications. For Health Canada approved PET radiopharmaceuticals like 18F-FDG, OH-CCO (on behalf of the MOH) provides coverage based on levels of evidence and specific PET Registries are established to aid in real-world evidence collection to inform OH-CCO regarding emerging PET applications. In the case of PSMA PET/CT, adapting this model to an IND PSMA PET/CT agent, 18F-DCFPyL, necessitated the creation of a hybrid Registry-Study model to leverage the existing OH-CCO Registry structure while respecting the need for a Health Canada Clinical Trials Application (CTA) for the deployment of this agent in the province. Within the first 2 years of the registry, over 1700 men have been imaged resulting in a change in management (compared to pre-PET management plans) in over half of the men imaged. In this article, we describe the organization and deployment of the PSMA PET/CT (PREP) Registry throughout the province to provide access for men with suspected prostate cancer recurrence along with key stakeholder perspectives and preliminary results.

There is significant overlap in the imaging characteristics of renal cell carcinoma (RCC) and oncocytoma, resulting in diagnostic uncertainty and unnecessary surgical resection. However, both oncocytomas and chromophobe RCC are known to be rich in mitochondria, compared to clear cell and papillary RCC subtypes. 99m Tc-sestamibi (MIBI) SPECT/CT scans localize within the mitochondria and have emerged as a potential imaging modality to further characterize renal masses. The goal of this study is to evaluate the utility of MIBI SPECT/CT imaging in the assessment and risk stratification of indeterminate renal masses.METHODS: A comparative study including 23 patients with indeterminate renal masses was performed. All patients had prior crosssectional imaging and underwent MIBI SPECT/CT imaging. MIBI SPECT/CT imaging characteristics including lesion density and MIBI uptake were correlated with histopathology from either percutaneous biopsy or surgical resection. Lesions with any degree of MIBI uptake were defined as positive and lesions with no uptake as negative (figure 1).RESULTS: 23 lesions were included with a median size of 3.2cm (1.8-6cm) and a density ranging from 22 to 56 Hounsfield Units. 20 of the lesions were solid enhancing masses and 3 were Bosniak 4 complex cysts with measurable solid components. Biopsy or postsurgical histopathology demonstrated 5 oncocytomas, 1 hybrid oncocytic/chromophobe tumor (HOCT) and 17 RCCs including 13 clear cell, 2 papillary and 1 chromophobe subtype. The median of mean and maximum relative tumor uptake in MIBI positive tumors (oncocytomas and HOCT) was 0.80 and 0.85, compared to 0.30 and 0.30 in cases with RCC, respectively. Using a mean relative tumor uptake of 0.5, all patients with oncocytoma and HOCT (100%) had positive MIBI uptake, and all RCC patients (0%) were negative.CONCLUSIONS: This study contributes to the growing literature indicating that MIBI uptake is a distinguishing imaging feature of low risk renal masses. The combination of presence or absence of MIBI uptake and lesions' density on SPECT-CT represents a novel imaging approach to risk stratifying incompletely characterized renal masses. Further validation of this technique may reduce the need for further imaging and unnecessary biopsy or surgical resection of indeterminate renal masses.

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